CLDN2

– IMU-856 is an Orally Available, Systemically Acting, Highly Selective and Potent Small Molecule Modulator of SIRT6 – – Targets Regeneration of Bowel Epithelium and Restoration of Intestinal Barrier Function – – Builds on Recently Released Phase 1b Data Showing Beneficial Effects in Celiac Disease Histology, Disease Symptoms, Biomarkers and Nutrient Absorption – – Virtual ePoster to be Presented Today, May 6, 2023, During 9:30 am - 4:00 pm CT Poster Session – NEW YORK, May 6, 2023 /PRNewswire/ -- Immunic, Inc. (Nasdaq: IMUX), a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases, today announced the presentation of clinical and preclinical data for IMU-856. Included in this presentation are new data on IMU-856's mode of action as a potent modulator of SIRT6 (Sirtuin 6), a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium. The presentation will be held as a virtual e-poster at Digestive Disease Week (DDW) 2023, currently underway through Tuesday, May 9, 2023, both virtually and in-person, in Chicago, IL. IMU-856 is a highly selective and potent small molecule which has been shown to modulate, stabilize and enhance expression of the SIRT6 protein, in particular, in the gastrointestinal tract. In the small intestine, SIRT6 expression is highest among absorptive enterocytes which are responsible for nutrient uptake, mucus-producing goblet cells which protect the wall's lining, and Paneth cells which support, protect and stimulate local regenerative stem cells. Modulation of these cell types by IMU-856 appears to direct local stem cells to divide and then differentiate into 'new' intestinal epithelial cells, thereby stimulating the natural physiologic process of renewal of the gut wall lining. In both animal and early clinical studies, IMU-856 has been shown to restore and renew the intestinal lining. In a preclinical DSS (dextran sodium sulfate) colitis model, IMU-856 treatment protected and also improved regeneration of the gut lining, as measured by normalization of crypt architecture. IMU-856 treatment also induced a dose-dependent tightening of the intestinal barrier, as measured by TEER (transepithelial electrical resistance) assay. Gene expression experiments revealed that this latter effect can at least be partially attributed to the upregulation of barrier forming claudin-1 and the downregulation of channel forming claudin-2. Finally, data from Immunic's phase 1b clinical trial of IMU-856, summarized in the company's May 4, 2023 press release, also corroborated these findings in a proof-of-concept trial in celiac disease patients. Immunic reported that IMU-856 treatment showed beneficial effects in four key dimensions of celiac disease pathophysiology: histology, disease symptoms, biomarkers and nutrient absorption. The observed effects included, not only protecting the gut against effects of the gluten challenge, but also highlighted improvements in gut health which are relevant to celiac disease and to other gastrointestinal diseases. The consistent signals of IMU-856 treatment in this trial, as compared to placebo, seem to support clinical proof for the regeneration and renewal of the bowel wall. "By restoring intestinal barrier function and bowel wall architecture through its effect on SIRT6, IMU-856 may offer a unique treatment option for patients suffering from gastrointestinal diseases," stated Hella Kohlhof, Ph.D., Chief Scientific Officer of Immunic. "Of particular interest, in preclinical studies, IMU-856 was shown to avoid suppression of immune cells and may therefore maintain immune surveillance for patients during therapy, representing a distinct advantage when compared with chronic administration of potentially immunosuppressive medications. Additionally, our preclinical studies showed that treatment with IMU-856 results in two important effects. First, the SIRT6 protein is stabilized, and second, de-acetylation of target structures by SIRT6 is prevented, leading to a regenerative phenotype." "Coming on the heels of the positive data we reported for our phase 1b clinical trial of IMU-856 in celiac disease, the presentation of earlier-stage findings at DDW, including announcing, for the first time, the mode of action of IMU-856, is an important step in our continued development process for this novel therapeutic," added Daniel Vitt, Ph.D., Chief Executive Officer and President of Immunic. "As recently reported, celiac disease patients treated with IMU-856 in the proof-of-concept trial showed a meaningful improvement in a wide array of key histologic, symptomatic, nutritional and immunologic parameters during gluten challenge, while IMU-856 continued to show a clean safety and tolerability profile. IMU-856 may also offer extensive potential beyond celiac disease including serious and widely prevalent gastrointestinal diseases with high unmet needs such as ulcerative colitis, Crohn's disease, or irritable bowel syndrome with diarrhea, all of which are characterized by compromised intestinal barrier function. That said, we are preparing for a phase 2b clinical trial of IMU-856 in celiac disease patients, while also considering other indications." Poster Details Franziska Buriánek, M.D., Senior Medical Director at Immunic, will present data from the single and multiple ascending dose portions of the phase 1 clinical trial of IMU-856 in healthy human subjects as well as preclinical data on IMU-856, including its mode of action, in a virtual e-poster at DDW 2023. Title: First-in-Human Trial of IMU-856, an Orally Available Regulator Of Barrier Function For The Treatment Of Celiac Disease ePoster Number: EP63 Session: AGA Celiac Disease and Gluten Related Disorders Date: Saturday, May 6, 2023 Time: 9:30 am - 4:00 pm CT (10:30 am - 5:00 pm ET) The poster is accessible on the "Events and Presentations" section of Immunic's website at: . About IMU-856 IMU-856 is an orally available and systemically acting small molecule modulator that targets SIRT6 (Sirtuin 6), a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium. Based on preclinical data, the compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, inflammatory bowel disease, irritable bowel syndrome with diarrhea and other intestinal barrier function associated diseases. Immunic believes that, because IMU-856 has been shown in preclinical investigations to avoid suppression of immune cells, it may therefore have the potential to maintain immune surveillance for patients during therapy, an important advantage versus immunosuppressive medications. IMU-856 demonstrated positive results in a phase 1b clinical trial in celiac disease patients in four key dimensions of the disease's pathophysiology: histology, disease symptoms, biomarkers and nutrient absorption. Currently, the company is preparing for phase 2 clinical testing in this patient population. IMU-856 is an investigational drug product that has not been approved in any jurisdiction. About Immunic, Inc. Immunic, Inc. (Nasdaq: IMUX) is a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases. The company's lead development program, vidofludimus calcium (IMU-838), currently in phase 3 clinical trials for the treatment of multiple sclerosis and which has shown therapeutic activity in phase 2 clinical trials in patients suffering from relapsing-remitting multiple sclerosis and moderate-to-severe ulcerative colitis, selectively inhibits activated immune cells and shows combined anti-inflammatory, anti-viral and neuroprotective effects. IMU-856 is targeted to restore intestinal barrier function and regenerate bowel epithelium, which would be applicable in numerous gastrointestinal diseases, such as celiac disease, where it is currently in preparations for a phase 2 clinical trial. For further information, please visit: . Cautionary Statement Regarding Forward-Looking Statements This press release contains "forward-looking statements" that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, sufficiency of cash, expected development, timing and results of clinical trials, prospects, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Immunic's development programs and the targeted diseases; the potential for IMU-856 to safely and effectively target diseases; the potential for IMU-856 to have applicability in the treatment of other gastrointestinal diseases; interpretation of preclinical and clinical data for IMU-856 and potential effects including the phase 1b clinical results of IMU-856; plans for phase 2 clinical testing of IMU-856 and the timing of other current and future clinical trials and anticipated clinical milestones; the nature, strategy and focus of the company and further updates with respect thereto; and the development and commercial potential of any product candidates of the company. Immunic may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Such statements are based on management's current expectations and involve substantial risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, the COVID-19 pandemic, increasing inflation, impacts of the Ukraine – Russia conflict on planned and ongoing clinical trials, risks and uncertainties associated with the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient financial and other resources to meet business objectives and operational requirements, the fact that the results of earlier preclinical studies and clinical trials may not be predictive of future clinical trial results, the protection and market exclusivity provided by Immunic's intellectual property, risks related to the drug development and the regulatory approval process and the impact of competitive products and technological changes. A further list and descriptions of these risks, uncertainties and other factors can be found in the section captioned "Risk Factors," in the company's Annual Report on Form 10-K for the fiscal year ended December 31, 2022, filed with the SEC on February 23, 2023, and in the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at or ir.imux.com/sec-filings. Any forward-looking statement made in this release speaks only as of the date of this release. Immunic disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. Immunic expressly disclaims all liability in respect to actions taken or not taken based on any or all the contents of this press release. Contact Information Immunic, Inc. Jessica Breu Head of Investor Relations and Communications +49 89 2080 477 09 [email protected] US IR Contact Rx Communications Group Paula Schwartz +1 917 633 7790 [email protected] US Media Contact KOGS Communication Edna Kaplan +1 617 974 8659 [email protected] SOURCE Immunic, Inc.

ROCKVILLE, Md. and SUZHOU, China, Oct. 30, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, announced that the first patient was dosed in Australia for its proprietary anti-Claudin18.2 monoclonal antibody-drug conjugate(ADC) (R&D code: IBI343) in Phase I clinical trial for the treatment of patients with advanced solid tumors. It is the first ADC candidate drug to enter clinical phase in Innovent's pipeline. The study (NCT05458219) is an open-label, multi-center Phase I study evaluating the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D). IBI343 is a recombinant human anti-Claudin 18.2 monoclonal ADC. After IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization occurred and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". In both Claudin 18.2 high and low expression mice tumor bearing models, IBI343 exhibited potent tumor growth inhibition efficacy, and it also demonstrated tolerable safety profile in preclinical in vivo models. Dr. Andrea Tazbirkova, Pindara Private Hospital Located in Queensland, Australia, stated： "Claudin 18.2 has emerged as an ideal anti-tumor target and has been clinically validated by different modalities including mono-antibodies and CAR-T therapy with manageable toxicity. Nonetheless, the efficacy is selective and limited within cancer patients with CLDN18.2-high expression, leaving unmet need for patients with CLDN18.2 low-expressing tumors. IBI343 is Claudin 18.2 targeting ADC with bystander effect and has demonstrated promising anti-tumor effect in Claudin 18.2-high and low in-vivo models with tolerable safety profile. We look forward to the positive results in the safety/tolerability and efficacy of IBI343 in the clinic." Dr. Hui Zhou, Senior Vice President of Innovent, stated: " At present, target treatment options are limited for gastric and pancreatic cancer where imply huge unmet clinical needs. High expression of Claudin 18.2 in aforesaid tumors suggests its high potential and Innovent has been actively rolling out a cluster of Claudin 18.2 drug candidates across different modalities to seek for differentiated therapeutic values while guarantee druggability. We are pleased that the first patient dose of IBI343 has been completed in Australia. In parallel, the IND for IBI343 has been filed in China last month. We are looking forward to the positive results of IBI343 in patients with advanced solid tumors. IBI343 is our first ADC molecule to initiate clinical study in both Australia and China, adding a valuable clinical asset in our R&D pipeline that represents Innovent's global innovation strategy. The company will also accelerate the development of more innovative molecules with high global potential, taking advantage of cross-regional R & D and clinical resources, adhering to the long-term development strategy of 'driven by innovation, developed through globalization'with an aim to benefit cancer patients worldwide." About Claudin 18.2 Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectal cancer. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors. Globally, there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products. However, currently no drug targeting Claudin18.2 has been approved. About IBI343 IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occurr and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". Currently, Phase I study of IBI343 has been conducted in Australia (NCT05458219) to assess the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune disease, metabolic disorder and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK. Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT (sintilimab injection), BYVASDA (bevacizumab biosimilar injection), SULINNO (adalimumab biosimilar injection), HALPRYZA (rituximab biosimilar injection), Pemazyre (pemigatinib oral inhibitor), olverembatinib （BCRABLTKI）,Cyramza (ramucirumab) and selpercatinib. An additional 2 assets are under NMPA NDA review, 4 assets are in Phase 3 or pivotal clinical trials, and 21 more molecules are in clinical studies. Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.